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Anglia Ruskin University ARU Featured PhD Programmes
Anglia Ruskin University ARU Featured PhD Programmes

What are the signalling events responsible for extracellular matrix-dependent breast cancer cell growth?


Department of Biomedical Science

About the Project

Due to the elevated cancer cell growth rate and the limited blood supply, the tumour microenvironment is often nutrient deprived. We recently demonstrated that the extracellular matrix (ECM, a complex network of secreted proteins) plays a different role in breast cancer cell growth under different nutrient starvations. On the one hand, we showed that under amino acid starvation, ECM internalisation and lysosomal degradation leads to changes in breast cancer cell metabolism, which promote cell growth. This indicate that the ECM represents a source of nutrients under amino acid starvation. On the other hand, we observed that the ECM is also able to support breast cancer cell growth under glucose starvation, but it does so without affecting cell metabolism. Interestingly, ECM-dependent cell growth under glucose starvation requires focal adhesion signalling, as indicated by the reduction in cell growth in the presence of a focal adhesion kinase inhibitor. These observations suggest that ECM-induced signalling is required to support cell growth in glucose-deprived environments.

Hypothesis and aims.
Here we hypothesise that cell-ECM interaction leads to the activation of pro-survival signalling pathways when the cells experience glucose deprivation. To investigate this we will:
1. Further characterise how cells respond to different glucose concentrations and what the ECM contribution is
2. As we already know that mTOR signalling is activated under glucose starvation in the presence of ECM, we will use this to identify the best time points to analyse changes in cell signalling
3. Use a phospho-proteomic approach coupled with mass spectrometry to identify the signalling pathways that are specifically up-regulated by the presence of ECM under glucose deprivation. The role of these will be further validated by analysing ECM-dependent cell growth when the identified pathways are inhibited
4. Use human breast cancer tissue sample to assess whether the identified pathways are up-regulated during breast cancer progression

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.

References

https://www.sheffield.ac.uk/biosciences/people/bms-staff/academic/elena-rainero

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